Multiple surrounded by a fatty, insulina-ting myelin

Multiple Sclerosis (MS) is a chronic multifactorial disease of the Central Nervous System (CNS) 5(1) characterized by «sclerosis» of different domains in the CNS and the presence of MRI-detected lesions called «scars» or «plaques» 6. MS is a major inflammatory and neurological disease affecting the white matter in the brain, spinal cord and optic nerves 1, 3(5). The substantial role of white matter is to contact impulses between the gray matter domains and the rest areas of an organism 3(8) and it consists of neuronal axons surrounded by a fatty, insulina-ting myelin sheath, which increases the speed of impulses across the axons 1, 3(8) and functions as a protective substance.

Destruction of the above insulinating sheath and degeneration of the cells that produce myelin leads to axonal loss 1 (Meffe et al, 2005), 9(2) and impair neurotransmission due to degeneration of neurons 7 (1). As a result and depending on the affected area of the CNS, a spectrum of various symptoms and disabilities can be manifested resulting in deficits of crucial functions of an organism 9(2), 11. Experts, also, highlight some other major hallmarks of the disease such as gliosis, blood-brain barrier (BBB) dysfunction 7 high infiltration of various cell types of immune system such as T cells, B cells, macrophages as well as secretion of pro-inflammatory molecules 8(1-3). The disease was first identified and characterized by Jean- Martin Charcot at the end of the 19th century and up to now millions of people affected worldwide 3(17). Based on the data referred to the Atlas of MS, the number of people that are diagnosed with MS increased around 10% globally from 2008 to 2013 either because of clearly developed diagnostic criteria or a bad and unhealthy lifestyle that people adopt it. However, the distribution of the disease shows different rates between distinct regions and distinct populations 12 (2), 5, 3(6) giving a substantially increased prevalence in countries that are far away from the equator 5,12. MS affects children and adults between 10 and 80 years of age 5, 12(3) but the onset of symptoms is recognized between 20 and 40 years of age with the female individuals being affected two times more frequently comparing with the males

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Multiple sensory impairments and ataxia 3. There is

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system that is characterized by inflammation, demyelination and axonal degeneration1.

The most common age of diagnosis is usually between 15 and 40 years, which is considered the prime age of career and family building2. The epidemiological profile of MS in Northern Jordan is similar to what is reported worldwide; with the prevalence of MS in Jordan estimated as 38/100,000 people3. The last mentioned epidemiological study reported that the most frequent symptoms are not different from those reported in the western countries and include weakness, optic neuritis, sensory impairments and ataxia 3.There is established evidence that highlights the multiple health effects of physical activity (PA) for people with MS (eg, physical fitness, quality of life)12-16.17. Regular PA may even have positive long-term effects on reducing the rate of disability progression (i.

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e. decrease in the progression of the disease).18 In addition, physical activity has been associated with improvements in fatigue, depression, quality of life, and walking mobility in persons with MS 5-8. However, several studies found that PA to be decreased in people with MS when compared with non-diseased population9-12.

Given the nature of the complexity of the disease, several factors may con¬tribute to the decreased level of physical activity level in this population. This may include; fatigue, weakness and poor coordination, decline in cognitive function, anxiety and depression. To better intervene and promote PA behavior in people with MS, it is crucial first to identify factors that are associated with PA level in this population. T The International Classification of Functioning, Disability and Health (ICF) model 4gives a useful framework for controlling factors associated with physical activity (Figure1). The model describe human functioning and disability in 3 domains (eg, body functions and structures, activity, and participation) as the result of the interaction of health conditions, personal factors, and environmental factors5. Using the ICF framework as a guide, determinants of physical activity that previously reported among individuals with disabilities and adults who were healthy can be classified as impairments of body functions and structures (e.g., disability, fatigue, depression, apathy, cognitive functions or type of MS), environmental factors (e.

g., social support, presence of heavy traffic or access to services), and personal factors (e.g.

, motivation, history of fall, age, self-efficacy, educational level, or employment status)6.Within the context of ICF at the level of body structure and function domain, several studies have examined the relationship between PA level and different variables of this domain, which included disability, fatigue, depression, apathy, cognitive functions and type of MS. There are however, a contradicting results of studies that assessed the relationship between PA level and fatigue (10, 16,21). Regarding depression, cognitive function, apathy, type of MS and disability these factors were less frequently examined variables 7,8,9,10,13,14,15, with inconsistency in findings regarding depression and fatigue10. This provide the indication that further research is needed in this area. At the level of environmental and personal domains systematic review found that employment status and educational level were frequently examined. However this systematic review reported that self-efficacy, history of fall, motivation, social support, presence of heavy traffic and access to services were less frequently examined and there is inconsistency in the results of these studies 21-26.

This provide the indication that further research is needed in this area. To summarize, to our knowledge few studies evaluated the correlations between physical activity level and body structure factors (including cognitive function, apathy, type of MS and depression), environmental variables(including social support, presence of heavy traffic and access to services), and personal factors (including self-efficacy, history of fall, motivation). Thus, we are in need for more research to explore the correlations of these variables with physical activity level in MS. Furthermore, we need to replicate these studies to see how body structures factors, personal factors and environmental factors interact between each other.

In addition, previous studies included minimally impaired MS or relapsing remitting MS, and did not include other types of MS. All these clinical characteristics (variables) were assessed separately and until now there is no study assessed all these variables together and how they interact between each other and how they correlate with PA and which one of these clinical characteristics are important and the most sensitive and strongly predict PA level in people with MS. This study aims to examine factors that may be associated with the low physical activity level in people with MS, and to determine which of these clinical characteristics are important to predict PA level in people with MS. By using the ICF model as a guiding framework this study will categorize variables according to body function and structure, activity, participation, personal and environmental domains.Figure.1Potential determinants of physical activity in people with multiple sclerosis are categorized using the International Classification of Functioning, Disability and Health model(ICF).

B-II: SIGNIFICANCE OF WORKThis study will be conducted with main aim of determining which of these clinical characteristics are important and the most sensitive to correlate with low physical activity level in people with MS. If the most sensitive factor that affects physical activity level is known, interventions targeting this factor may help in improving physical activity level in people with MS. Consequently, improvement in physical activity level could improve overall quality of life and participation in MS. As a result, this might decrease the time spent in therapeutic sessions and reduce the economical health-care demands.

CAPPROACH AND METHODOLOGYC-I: METHODOLOGYStudy design:This will be a cross-sectional study to investigate the factors that predict physical activity levels in people with MS. Physical functioning factors, personal factors and environmental factors will be tested and the relationship between these variables will also be explored.Recruitment:One hundred MS patients attending routine neurology clinic appointments at King Abdulla University Hospital (KAUH) or Princess Basma Hospital will be screened for eligibility by a neurology consultant; the clinician who is responsible for their care. Eligible subjects will be invited to participate in the study. Additionally, brochures and adverts about the study will be distributed through the Jordanian Multiple Sclerosis Society; subjects who are willing to participate will also be screened for eligibility by a neurology consultant at the KAUH.

Inclusion criteria for the MS patients:1) Age above 18 years.2)Multiple sclerosis (MS) of any type (relapsing remitting, primary progressive, secondary progressive).3) Clinically diagnosed with MS according to McDonald Criteria11.4) Capacity to give informed consent.5) No exacerbation of symptoms 30 days prior to completing testing.

Exclusion criteria for the MS patients:1) Patients who had a relapse within 4 weeks before the study.2) Other neurological disease.Outcome measures:Body Structure and Function Domain:1-Disability:will be measured using the Patient Determined Disease Steps (PDDS) scale 30. The PDDS is a self-report questionnaire that contains a single item for measuring disability using an ordinal scale from 0 (normal) through 8(bedridden). This scale was developed as an inexpensive surrogate for the Expanded Disability Status Scale (EDSS) and scores from the PDDS are linearly and strongly related with physician-administered EDSS scores (r=0.87).

312-Fatigue and depression: will be evaluated using the fatigue severity scale 32. while depression will be evaluated using the Beck Depression Inventory- version II (BDI-II) 33.3-Cognitive outcome measures: an international expert consensus committee recommended a brief battery of tests for cognitiveevaluation in multiple sclerosis 39. The Brief International Cognitive Assessment for MS (BICAMS) battery includes tests of mental processing speed and memory:A-The brief visuospatial memory test45 is recommended and valuable assessment tool for visual memory (immediate recall) in which participants are asked to draw a display of six geometric figures that is presented over three learning trials. Then the participants will be asked to draw the display from memory this test show its validity from its strong association with some brain lesions 35.B-The Symbol Digit Modalities Test19 is the test for information processing speed.

. This test asks participants to quickly say the number that matches a corresponding symbol. Following a 12 minute delay, the participant will be asked firstly to complete one line from the test by filling in the number associated with the symbol from memory and secondly will be asked to complete all 6 lines of the test by saying the number that matches the symbol. The test has sensitivity of 82% and specificity of 60% , and high sensitivity for cognitive impairment in MS people.

Moreover it shows validity in many countries 35.C- The California Verbal Learning Test-II (CVLT-II)40: this test for verbal memory (immediate recall) comprises a 16-item word list, with four items belonging to each of four categories, arranged randomly (Figure 2). The list is read aloud five times in the same order to the patient, at a slightly slower rate than one item per sec¬ond. Patients are required to recall as many items as possi¬ble, in any order, after each reading of the list. The CVLT-II T1-5 can be completed in 5–10 min, including instructions, testing and responses.444-Apathy: Apathy Evaluation Scale (AES):a questionnaire including 18 items concerning behavioral (items 2, 6, 10, 11, 12), cognitive (items 1, 3, 4, 5, 7, 9, 13, 16), emotional (items 8, 14), and other (items 15, 17, 18) aspects of apathy.

All items are scored on 4-point Likert scale (to mean “not at all true”, “slightly true”, “somewhat true” or “very true”; scoring is reversed for items 6, 7, 11 because of the way they are written). The total score ranges from 18 to 72 points (higher scores indicate more severe apathy).51Activity Domain:1-Walking impairment: Multiple sclerosis walking scale this patient-based scale is shown to be reliable and valid, and more responsive than other scales measuring walking abilities.

37 coefficient alpha was .96 for the MSWS-12.3810 meter walk test 6 minute walk test Personal Domain:1-Self efficacy:a- Exercise Self-efficacy (EXSE) :The scale was developed to assess exercise self-efficacy in older adults but has been validated for use with the MS population 42. EXSE assesses self-efficacy longitudinally, examining confidence in physical activity over time. 432-History of fall: participants will report the number of falls and near falls that occurred over the past 3 months. They were instructed that a “fall” was any unexpected loss of balance that resulted in whole body contact with the ground 44 and that a near fall 45 was any unexpected contact with an environmental object (e.

g., wall, piece of furniture, person) that prevented a fall to the ground. This is a common way to measure fall history among people with MS. 46,473-Motivation: Motivation for Physical Activity and Exercise questionnaire OR The Exercise Motivations InventoryEnvironmental Domain:1-Social Support.a- The Social Support for Exercise Scale (SSES) 35 consists of twelve questions to separately evaluate the role of both family (or members of the household) and friends in providing the participant with support for their exercise behavior over the previous three months. Each support statement is rated on a scale from one (never) to five (very often) and then summed for a total family support score and a total friend support score. The SSES has been found to be both a reliable and valid measure of family and friend social support.

39 The internal consistency of the family and friend subscales were .86 and .91 respectively.ORb- Global perceptions of social support will be measured by the 24-item Social Provisions Scale (SPS). Scores from the subscales are summed to form a single composite measure of social support. There is evidence that SPS scores provide a reliable and valid measure of global perceptions of social support (40). The internal consistency estimate for the composite SPS score based on coefficient alpha in this study was 0.83.

41Presence of heavy traffic, access to services: The IPAQ-E includes seven core items, four recommended, and six optional items. The seven core items measure the structural components of the environment including the type of housing in a person’s neighbourhood along with items that pertain more to walking and bicycling behaviors such as the presence of sidewalks, amenities, and recreation facilities. The four recommended items measure other related components of the environment including traffic and aesthetics49. There is preliminary evidence supporting the reliability and validity of IPAQ-E scores in a random sample of adults 50.Participation Domain:1-Physical activity :will be measured subjectively by the Godin Leisure-Time Exercise Questionnaire (GLTEQ) and objectively by the ActiGraph single-axis accelerometer(model 7164 version, Health One Technology, Fort Walton Beach, FL).

The GLTEQ is a simple, reliable, and valid measure of physical activity that has been widely used in epidemiologic, clinical, and behavioral change studies. There is evidence that scores from the GLTEQ and accelerometer provide valid measures of physical activity in individuals with MS. Previous researchers reported a moderate-to-strong correlation (r =0.52) between the total leisure activity score from the GLTEQ with total movement counts from the ActiGraph accelerometer in a sample of 30 individuals with MS. 48Table1: summery of outcome measures used in the studyDomain Trait Outcome measureBody Structure and Function Disability Determined Disease Steps (PDDS) scale Fatigue fatigue severity scale Depression Beck Depression Inventory- version II (BDI-II) Apathy Apathy Evaluation Scale (AES): Cognitive functions A-The brief visuospatial memory test ,B-The Symbol Digit Modalities Test, C- The California Verbal Learning Test-II (CVLT-II) Type of MS Will be assessed (diagnosed) by neurologist.

Activity Walking impairment Multiple sclerosis walking scale (MSWS)Personal factors Motivation ??? History of fall, Number of falls and near falls that occurred over the past 3 months Self-efficacy Exercise Self-efficacy (EXSE)ORMarkus Self-Efficacy for Physical Activity Scale (MSES) Demographic Age, gender, height and weight, co-morbidities, medications, EDSS, duration of the disease. Employment status Educational level Environmental factors Social support The Social Support for Exercise Scale (SSES) OR Global perceptions of social support Presence of heavy traffic, Access to services IPAQ-EParticipation Physical activity levels -Objective measures derived from mobility monitor (Actigraph)- Subjective measures derived from Godin Leisure-Time Exercise Questionnaire (GLTEQ)


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